Neovascular ocular diseases as exemplified by retinopathy of prematurity (ROP), proliferative diabetic retinopathy (PDR) and "wet" age-related macular degeneration (AMD) are severe diseases affecting all age groups in the US. Recently, there has been progress in neovascular ocular disease drug therapy based on large molecule VEGF inhibitors. Nevertheless, novel drug therapies are needed that i. have new mechanisms of action ii. are highly efficacious iii. are amenable to less invasive ocular administration and iv. are highly cost effective. We believe that this need will best be met with classical small molecule synthetic organic drugs that can be manufactured at low cost and have high transcleral permeability. This proposal centers on just such a small molecule anti- angiogenic compound, carboxyamidotriazole (CAI). CAI has a novel mechanism of action, demonstrated efficacy in mouse ocular neovascularization models and has transcleral permeability. Herein, we aim study the potential of CAI to treat neovascular disease by ocular delivery. To this end in Phase I we will i. develop ocular formulations of carboxyamidotriazole (CAI) ii. test the anti-angiogenic effects of CAI in human retinal endothelial cells and iii. test the intravitreal ocular efficacy and safety of optimal CAI formulation(s) in the OIR model and choroidal neovascularization (CNV) models. Novel drug therapies are needed that have new mechanisms of action are highly efficacious and amenable to less invasive ocular administration while being highly cost effective. We believe that this need will best be met with classical small molecule synthetic organic drugs that can be manufactured at low cost and have high transcleral permeability. [unreadable] [unreadable] [unreadable]